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Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease)

Kar-Ming Fung, M.D., Ph.D.

Department of Pathology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
Last update: March 31, 2007

Summary: Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease) (LDD) is a condition featured by disorganized cerebellar folia leading to characteristic, thickening of the cerebellar folia. It has features of both malformation and neoplasm. LDD is discovered typically in the 3^rd and 4^th decades and is associated with Cowden syndrome and linked to germline mutations in PTEN gene.

Behavior: Biologically, this lesion is benign (WHO grade I). Although they appear to be non-neoplastic in nature, but progressive and gradual enlargement has been demonstrated. LDD behaves like a slow growing benign tumor. Gross total resection is the treatment of choice. Recurrence may occur.

Age and Sex: Usually discovered in the 2^nd or 3rd^rd decade. But the spectrum of age is wide and congenital cases have been described.

Incidence: Rare.

Location: Cerebellum.

Association:

Associated with Cowden syndrome.
Rare cases have been associated with astrocytic neoplasms at a different location or non-neoplastic abnormalities of the CNS (including heterotopias, olivary nuclear hypertrophy, hydromyelia and syrinx).

Genetics and Molecular Pathology: Autosomal dominant, due to germline mutation of PTEN on chromosome 10q23 (Genetic changes of Cowden syndrome). The activation of the PTEN/AKT/mTOR pathway and suggesting a central role for mTOR in the pathogenesis of LDD.^{1, 2}

Clinical Features: The most common manifestations are those related to obstructive hydrocephalus and intracranial hypertension. Other manifestations include cerebellar signs such as ataxia and deficits of cranial nerves. They may also be incidental findings.

Imaging Features:

The salient macroscopic feature of LDD on cross section is thickening of the folia. On MRI images, this pattern is transformed into a pathognomonic "tiger-stripping" laminations of alternating T1/T2-isointense and T1-hyperintense/T2-hypointense laminations in reference to cerebellar gray matter. This pattern can also be recognized by high resolution CT scans.
No contrast enhancement for most cases.

Gross Pathology: LDD is characterized by regional, obvious thickening of the cerebellar folia. The thickening is usually quite homogeneous which makes LDD look like "exaggerated" or "giant" folia on gross examination. The gray folia do not appear like normal gray matter but appear rather firm and pale due to the presence of abnormal white matter.

Histology: [Click here to see a slide of LDD]

The histology looks like an "inside-out" architecture of the cerebellum. A layer of myelinated fibers with large diameter myelinated axons is present in the molecular layer. The internal granule layer is replaced by intermediate sized to large dysplastic neurons. The larger, ganglion-like cells have morphological resemblance to Purkinje cells to a certain extent. Nissl substance is present, particularly, in the more mature lesions. The degree of replacement is variable. Residual internal granule cells can be seen in the deeper part of the lesion.
The presence of mitotic figure is exceptional.
Normal Purkinje cell layer is disrupted.
The native white matter of the folia is atrophic and rarefied.

Immunohistochemistry:

The histologic features are very specific. Immunohistochemistry is not typically required for diagnosis.
Ki-67 labeling is 0-2% for the small number of cases that have been studied.

Differential Diagnosis:

The imaging, gross and histologic features are very characteristic and LDD are usually no confused with other entities.

Reference:

Zhou XP, Marsh DJ, Morrison CD, Chaudhury AR, Maxwell M, Reifenberger G, Eng C. Germline inactivation of PTEN and dysregulation of the phosphoinositol-3-kinase/Akt pathway cause human Lhermitte-Duclos disease in adults. Am J Hum Genet. 2003 73(5):1191-8.
Abel TW, Baker SJ, Fraser MM, Tihan T, Nelson JS, Yachnis AT, Bouffard JP, Mena H, Burger PC, Eberhart CG. Lhermitte-Duclos disease: a report of 31 cases with immunohistochemical analysis of the PTEN/AKT/mTOR pathway. J Neuropathol Exp Neurol. 2005 64(4):341-9.